Thrombin, thromboplastin and phospholipids are all common ingredients in reagents used for coagulation assays performed on samples of serum and plasma. Thrombin and thromboplastin in particular, are very sticky substances and are difficult to remove from a surface. Because of this property, it is difficult to avoid cross contamination of a second sample by the reagent used in one test that is still adhering to the probe that is then used to deliver a different reagent to a second sample. Cross contamination of a reagent for one assay into a reagent for another assay or into a sample will adversely affect assay results.
This was not a problem when all coagulation assays were done manually, as separate pipettes were used with each reagent and with each sample. A pipette was discarded after each use, thereby eliminating cross contamination problems.
Today, many coagulation assays are performed on analyzers. In most analyzers that have limited random access capabilities, cross contamination problems are avoided by having dedicated fluidic pathways for each reagent. By doing so, the same reagent is constantly dispensed by the same probe or pipette, generally in the same order for a large batch of serum or plasma samples having the same test run. Therefore, the probe or pipette does not have to be cleaned, or cleaned well, between each dispensation of reagent, as the probe or pipette will always be dispensing the same reagent.
However, the next generation of automated coagulation analyzers contains random access capabilities. This means that a limited number of probes attached to fluidic pathways will be dispensing a different reagent into each separate sample container, if the analyzer is so programmed. Automated analyzers that have random access capabilities are therefore subject to cross contamination problems. For example, the presence of thrombin from a fibrinogen assay and thromboplastin from a prothrombin assay on a probe results in a shortening of a samples clotting time in the activated partial thromboplastin time assay. Thrombin, thromboplastin and fibrinogen are particularly difficult to remove from a surface because of their strong adhesion properties. Changes in assay results would affect the diagnosis afforded a patient, thereby causing severe ramifications to the patient's treatment.
Currently, there are some types of cleaners available that remove carryover. These are strong denaturing cleaners, such as sodium dodecylsuifate, 10% bleach solutions or hydrogen peroxide solutions. Although they do remove carryover, these cleaners also denature the reagents at the same time, resulting in poor assay performance results. This occurs because the denaturing cleaners also remain on the probe and are carried back to the reagent vials or are mixed with the reagent as it enters the bore of the probe, prior to the dispensation of the reagent. Therefore, not only must each reagent be thoroughly cleaned from the probe, it must be rapidly cleaned in order for the probe to be able to dispense reagent into a large number of samples in a very short amount of time, for example, 180 samples per hour.
A fully automated coagulation analyzer with random access capabilities to perform analyses related to hemostasis and thrombosis on serum and plasma samples uses common pathways for reagents, thereby necessitating a substantially non-denaturing cleaning solution for the common reagent pathway, the probe.
Therefore, it is highly desirable in the art to have a solution for cleaning a reagent probe from residual coagulation assay reagents, in particular, thrombin, thromboplastin and fibrin, in order to avoid any contamination from the carryover of a reagent from one sample tube to another.